From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
IgE
Multiple
Myeloma
By Ben
G. Fishkin,
David
Natalie
T. Borucki,
of
Orloff,
and
Hans
the
Louis
Third
Case
E. Scaduto,
L. Spiegelberg
The third
known
case of IgE multiple
myeloma
is described.
The patient
was
a 65-yr-old
woman
who
died
11 mo
after a diagnosis
of multiple
myeloma
The light-chain
type
of the myeloma
protein
was k in contrast
to X of the
other
two IgE myeloma
proteins.
Her
clinical
manifestations
differed
from
was made
by a surgical
biopsy
of the
left iliac
crest.
Her serum
contained
approximately
2.7 g/100
ml of a paraprotein
of mid-y
mobility.
The isolated
anomalous
protein
gave a reaction
of
identity
with the lgE myeloma
protein
of the second
reported
case when
reacted
with
a specific
IgE antiserum.
the two previously
reported
cases
in
several
respects.
She
had
neither
plasma
cell leukemia
nor overt Bence
Jones
proteinunia
and developed
rapidly progressive
widespread
osteosclerotic lesions
that were associated
with
bone pain.
I
SHIZAKA
ET
globulins,
called
antibody,
nich3
etc.2
makes
reported
4.5 g/100
globulin
by
siderable
A-type
third
IgE
prior
cases.
Department
plasma
patient,
Pathology,
of
of
of both
report
contained
immunoabout
St.
California
Hospital
School
Scripps
cases
Hospital,
of
and
some
and
con-
with
the
the
two
from
(Wadsworth),
Santa
Medicine,
Clinic
had
lesions,
differed
7ohn’s
myeloma
been
re-
is concerned
manifestations
Pathology,
June
7, 1971;
revised
by grants
from
the
Division,
is
Special
Grant
publication
No.
and
Research
Foundation,
C.
Fishkin,
Ben
(Wadsworth),
and
Medicine,
Los
Santa
Angeles,
Monica,
Santa
Monica,
Calif.
Santa
Monica,
Calif.
Blood,
This
Services,
fever,
Los
Monica,
Los
Calif.;
Angeles,
Research
Calif.;
Foundation,
La
Calif.
This
Cancer
University
serum
normal
IgE
information
of skeletal
Administration
Medical
Experimental
whose
features
absence
Veterans
and
reaginic
as hay
However,
IgE multiple
case
(Sha)
has since
proteinuria.
Service,
immuno-
concentration
of IgE, of about
In 1967,
Johansson
and
Ben-
myeloma
clinical
clinical
human
such
identical
to the
considerable
leukemia,
whose
of
well-established
sensitivities
multiple
The
cell
Jones
Laboratory
of
Submitted
Supported
Research
with
class
the
of allergic
has been
accumulated.
only
a single
additional
Bence
Department
pital,
with
serum
the low
very
arduous.
(N.D.)
Laboratory
Calif.;
Clinic
a new
identical
et al. in 1969.
myeloma
the
From
Angeles,
fornia
In normal
its study
as
Ogawa
similarities:
Jolla,
is
a variety
a patient
striking
and
DESCRIBED’
that
ml of a paraprotein
antigenically
described
by Ishizaka.4
Subsequently,
IgE immunoglobulins
is extremely
rare,
ported
HAVE
IgE,
mediates
dermatitis,
g/100
ml,
50
AL.
which
atopic
.
: A Report
Foundation,
Society
(PRA
No.
510
M.D.:
August
Veterans
from
the
La
Jolla,
Chief,
Clinical
and
531,
accepted
September
American
American
Heart
Association
Department
of
Experimental
1,
Cancer
No.
Calif.
Cali-
No.
70-710.
Pathology,
of
Service,
Pathology,
Veterans
University
Scripps
Administration
of
Natalie
Orloff,
M.D.:
Associate
Pathologist,
Calif.
Louis E. Scaduto,
M.D.:
Attending
Physician,
David
T. Borucki,
M. 0.: Associate
Pathologist,
Hans
L. Spiegelberg.
M.D.:
Associate
Member,
Jolla,
Society,
Grant
and
Faculty
Research
Associate
Hospital
California
Calif.
La
1971.
Calif.
Laboratory
Professor
1971;
9,
Administration,
School
St.
St.
St.
John’s
John’s
Hospital,
John’s
Hospital,
Scripps
of
of
Hos-
Clinic
the
and
American
38).
Vol. 39, No. 3 (March), 1972
361
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
362
FISHKIN
CASE
A 65-yr-old
woman
investigation
sive
of
weakness,
to
be
5.0
The
had
weeks
nose
Her
in
1963,
a
the
present
cell
75%
grade
was
37%,
sec
(control
acid
progres-
was
became
for
found
aware
that
blood
of
subsided
from
a spon-
blast,
gave
creatinine
X-ray
present.
films
mg,
a total
of the
serum
skull,
demineralization
the
spine,
bony
8.4
12
2.7
albumin
3.8
g,
globulin
2.7
g/100
and
and
long
was
mg,
King-Armstrong
plasma
pelvis,
and
time
phosphorus
g,
was
Labstix
mg,
or
thorax
3%
rate
by
was
gamma
viscosity
thorax,
of
of
g, and
mm;
50 nucleated
prothrombin
9.5
protein
0.9
The
62,000/cu
metamyelocytes,
The
calcium
ml.
two
Ecchymoses
sedimentation
phosphatase
globulin
felt.
determined
test.
mg/100
basophils;
The
a
time,
palpable
platelets,
as
this
unremarkable.
4%
protein
guaiac
1.2
Relative
also
2%
formations.
8.6
was
was
and
alkaline
g, beta
was
18%;
in
for
At
acid
liver
myelocytes,
for
disclosed
was
3%
a 3+
serum
edge
eosinophils,
was
The
0.7
spleen
of
colectomy
uric
The
hematocrit,
2%
stool
ml.
patchy
1%
the
attack
bruisability
in 1966.
examination
ml;
rouleaux
The
and
an
easy
segmental
woman.
The
negative
globulin
performed.
protein,
Fundoscopic
g/100
in 1951,
of
respectively
pale
and
The
spike
for
margin.
with
electrophoresis
alpha1
volume
long
bones
bones
but
ml.
studies
demonwere
not
significant.
number
of
iliac
(0.1
3,
A
the
widespread
pancytopenic.
Five
hemoglobin
700
phosphatase
had
decreased
a setting
of
of
dull
on
patient
X
was
June
7;
0.83
5
the
June
mg/kg
KA
decrease
earlier
per
she
was
in
A skeletal
the
density
dose
8)
of
was
total
to
and
the
upper
of
13.0
mg
administered
of
89,000/cu
mm.
femoral
g/100
ml
on
6 for
on
May
an
attendant
20.
The
coarse
which
were
20.
dose
May
areas.
cells
globulin
April
a total
on
white
alkaline
and
cyclophosphamide
with
mm,
regions,
red
was
The
The
protein
disclosed
packed
She
discharged
femoral
survey
units
to
hospital
leu-
weakness,
transfused.
600/cu
the
upper
X-ray
of
of
bleeding.
May
ml.
therapy
14.
were
was
on
cells
g/100
because
because
serum
patient
readmitted
of
1100
to
reinstituted
of
Four
a hemoglobin
X
the
pelvic
mg
4000
226
The
was
March
108
packs
from
from
units.
in
a total
day
platelets
pains
examination.
with
20,
therapy
on
hospital
platelet
whereas
of
11.5
allopurinol
gastrointestinal
12
respectively.
state
47
discharged
to
day)
aching
was
ml,
units,
ml,
the
and
and
neutrophils
KA
38
g/100
per
a mottled
present
From
to
a pancytopenic
phosphatase
g/100
absolute
3.1
cells
dose
the
aggregates
plasma
and
hospital
to
ecchymoses,
red
12.0
the
in
with
to
20)
A
decrease
infiltrated
X
a total
readmitted
unsuccessful.
and
hemoglobin
day
from
were
well-differentiated
the
per
after
and
to
mg/kg
of
complained
alkaline
5.5
and
and
mg/kg
was
packed
increased
(0.067
Because
of
1300,
to 6.9
Melphalan
Hea
heavily
of
raised
discharged
sites
thinning
was
foci
cells
0.067
was
petechiae
from
to
4;
different
moderate
marrow
discontinued
patient
units
ranged
from
red
X
was
later,
tachycardia,
day
to
although
packed
patient
melphalan
week
The
cells,
of
per
and
April
kopenia.
units
from
a mild
trabeculae.
plasma
mg/kg
instituted,
aspirations
revealed
bone
Four
Melphalan
mg.
marrow
biopsy
differentiated
present.
On
bone
cancellous
poorly
were
day
negative
was
tests.
sec).
at
the
of
onset
and
adenocarcinoma,
urine
mg/100
crest
been
1970
of
pruritis
hepatitis
the
oophorectomy
cells;
The
g, alpha.
an
lymphocytes,
blood
attempts
in
5,
she
a cup
serum-induced
a comfortable
mm
io%
left
now
and
urine
12,700/cu
mobility
Three
40
1964,
5.0
12
of
hyperuricemia,
hemoglobin,
surgical
had
episode
costal
minimal
cells
lost
abdomen.
Serum
0.3
were
March
because
hemoglobin
when
had
and
11.9
units.
considered
of
admission
she
persistent
the
acid
uric
not
to
admission
right
white
and
strated
prior
before
the
(Wintrobe).
11.8
were
mo
I polyploid
neutrophils,
mid-y
Her
generalized
arms
sulfosalicylic
A
tachycardia.
had
revealed
were:
cells/100
(KA)
on
(LES)
she
the
count,
globulin
6
below
on
mm/hr
20%
and
Hospital
physician
admission
an
in
and
data
stabs,
her
before
subsequent
examination
fingerbreadths
red
3 wk
ulcer
hematocrit
white
John’s
consulted
exertion,
until
disclosed
and
Physical
80
well
and
duodenal
laboratory
on
months
history
tumor
were
been
later
1953
Brenner
to St.
had
bleed.
past
gout
admitted
She
dyspnea
Two
taneous
REPORT
ml.
weakness.
several
was
anemia.
fatigue,
g/100
patient
some
(Hea)
a severe
El AL.
of
She
serum
trabeculae
had
given,
not
and
27.
(1.66
decrease
mg/kg
per
in
the
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
MULTIPLE
MYELOMA
363
3/6/70
Fig. 1.
X-ray film
bone
55
Evolution
of pelvis
pain.
edge
On
was
KA
ml,
the
and
a total
was
It
associated
Narcotics
with
phosphatase
50
a
63%
uptake
osteosclerosis
fluoride
(18F)
units
of
was
65%
neutrophils.
For
pain
14.1
muscle
months
trophoresis
were
identified
were
and
a
autopsy
IgEk,
U
of
and
with
was
home
not
of
(BGF)
urine
contained
allopurinol.
blood
on
mid-y
February
cell
and
February
an
Serum
or
gel
concentrated
diffusion
mobility
12,
20,
count
1971
plasma
where
she
serum
demon-
discharge,
expired
with
of
migratory
bone
and
agonizing
thigh
X-rays
and
k chains.
demon-
inner
Serum
urine
samples
Elevated
January
the
on
thighs
dcc-
protein
except
time
was
uric
4 to
normal
at
hemo-
mm
anomalous
cell
Five
the
2700/cu
Serum
from
radio-
joints.
on the
muscle.
was
X-rays
sodium
Skeletal
The
mg/day
A
knee
count
spike.
blood
immature
of
16.
(20-40
alkaline
scan
A
both
femurs
of
ankles.
the
dysfunction.
1).
palpable
femoris
ml
and
and
liver
recurrence
1971.
An
incapacitating.
fractionation.
day
X
of
February
acid
January
for
an
discharge
22.
An
performed.
MATERIALS
double
the
nodules
quadriceps
day
Hospitaliza-
feet
Bengal
cell
a
December
The
the
was
symptoms.
was
ml,
in
upper
on
mg/100
was
in
per
29.
the
(Fig.
white
and
Prednisone
administered.
of
Rose
the
but
10
feet
isoenzyme
14,
mm,
the
mg/kg
July
hepatocellular
August
on
0.83
mg/100
concentration
Subcutaneous
invading
liver
hemoglobin
extremity
skeleton
pelvis,
The
lucency
the
and
7.3
1311
mild
admission
sclerosis.
myeloma
us
to
comfortable,
cage,
hospital
were
red
convalescent
of
the
blood
nucleated
was
was
entire
47,000/cu
a return
one
reduced
3
occasional
to
to
as
levels
22)
a
of the
disclosed
demonstrated
submitted
On
thoracic
prompted
a progression
biopsied
and
transfused.
lower
edema
acid
with
the
rare
through
ankles
An
increased
patient
shoulders,
the
according
an
platelets
the
the
cramps
strated
were
ml,
uric
virtually
were
g/100
nondependent
compatible
revealed
cells
a
a
3;
X
17
and
serum
anemia.
phosphatase
cells,
day
July
to
Admission
7.
pancytopenia
type
red
per
from
moved
of
alkaline
with
packed
July
a paraprotein.
was
scan
red
several
hepatic
reveal
that
bone
involving
The
involving
packed
globin
of
not
on
and
and
relief.
units
did
showed
of
knees
serum
sclerosis
mg/kg
lesions.
because
The
of
administered
erythema
for
KA
electrophoretogram
strated
the
4 U
(1.66
31. because
in
hospital
a mottled
discharged
was
the
palpable.
After
was
mg
July
required
to
longer
femurs.
800
started
were
admitted
no
demonstrated
patient
on
that
diffuse
osteosclerotic
no significant
alterations.
cyclophosphamide
of
required
pain
was
of
dose
intense
again
was
upper
the
course
for
was
spleen
studies
and
g/100
tion
the
X-ray
Another
10)
1 she
but
bones
12.9
of widespread
(3/6/70)
shows
July
felt,
units.
pelvic
8/1/70
urine
according
were
to
AND
analyzed
the
method
by
of
METHODS
microimmunoelectrophoresis6
Ouchterlony.7
A
and
sheep
antiserum
by
agar
to
the
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
364
FISH KIN El AL.
CELLULOSE ACETATE
I
1
NHS
Hea 2/3/1911
+
UREA STARCH GEL pH 3.5
IgE
RalgE
I
BJP
+
Fig. 2. Analysis
by cellulose acetate
and starch
gel
electrophoresis
of
normal
human
serum
(NHS),
serum
(Hea),
isolated
IgE, reduced
and
alkylated lgE (Ra lgE),
and
isolated
urinary
Bence
Jones
protein
(BJP) of patient
Hea.
STARCH GEL pH 8.8
NHS
Hea
-
+
IgE
myeloma
kindly
and
k
protein
provided
by
Dr.
and
H.
IgA,
described
tion
by
of
the
buffer
of
was
technique.
8.0
the
and
IgG
for
contained
study,
no
microzone
M
The
IgE
ture
at
twice
to
using
about
3%-5%
to
gel
formate
myeloma
M
of
IgC.
the
recrystalized
was
of
the
iodacetamide
to
also
used
in 0.5
M
1 hr
The
protein
further
was
out
a 0.05
to
tris
8.0.
of
carry
the
pH
cellulose
M
examine
buffer
the
pH
8.2
alkylated
at
isolated
M
the
by
phosphate
same
buffer.
myeloma
protein
isolated
IgE
serum
was
made.
myeloma
available
A
Beckman
electrophoresis.
buffer
pH
isolated
myeloma
for
at
1 hr
as
a modifica-
was
acetate
glycine
adjuvant.8
by
IgE
as
diffusion
0.005
the
well
respective
radial
with
and
as
the
patient
amount
and
in
the
against
buffer
were
Center
IgD,
quantitated
a small
either
dithiothreitol
for
also
Sha5
Freund’s
by
of
buffer
only
used
was
M
complete
and
with
equilibrated
this
myeloma
was
reduced
0.02
into
dialyzed
phosphate
1gM,
injected
column
IgE
IgA,
protein
with
protein
Reference
goats
were
was
Since
myeJoma
determined
urine
myeloma
employing
buffer11
IgC,
were
column
0.015
apparatus
protein
a concentration
or
serum
the
purify
urea
for
rabbits
in
IgE
electrophoresis
8 M
specific
a DEAE-cellulose
from
eluted
attempt
starch
0.05
The
eluted
electrophoresis
Vertical
chains
IgE
Immunoglobulin
incorporated
The
applied
was
subsequently
protein
Light
the
Health
concentrations
chromatography.
pH
Most
et al.9
Mancini
protein
serum
to
of
from
Jones
IgD
Mancini
DEAE-cellulose
obtained
Bence
and
antiserum
Institutes
Antisera
were
or
1gM,
a rabbit
National
respectively.
chains
proteins
IgG,
and
the
Grey,
X light
myeloma
ND.3
by
a concentration
or
5510
a
protein.
room
temperaof
0.05
M
cold.
RESULTS
Cellulose
tained
on
acetate
February
and
3,
starch
1971
gel
are
shown
electrophoretic
in
Fig.
patterns
2.
The
former
of
the
serum
demonstrated
ob-
a
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
MULTIPLE
MYELOMA
monoclonal
protein,
365
band
of medium
or approximately
Bence
Jones
to the
light
protein
tatively
per 100
the serum
ml, and
specific
antisera
diffuse
precipitin
with
of the
the
arc
anti-IgG,
IgA,
and
not
different
and
As
can
be
myeloma
and the
but
not
seen
of the
3,
second
patient
protein
concentrated
with
in the
urine
(urine
layered
tate
in Fig.
buffered
Hea
anti-’
antisera.
over
urine
10
antisera
indicative
formed
a line
immunodiffusion
ml
00
concentrated
of
HC1;
bath)
and
p-toluene
for
Bence
a broad
precipitin
antigen
with
the
no
IgE
acid;
protein
immuno-
against
the
myeloma
for K light
protein
chains
of light
chains
chains.
A
To
anomalous
analysis.
prepared
isolated
specific
arcs
excess.
patient
with the
to Ouchterlony
sulfonic
Jones
Quantimg of 1gM
employing
20
quantiation
chains
K
faint
IgE
antiserum
(N.D.).
Both
the
with
the antisera
Radial
in a water
an
identical
protein.
revealed
of identity
using
serum
isolated
a mobility
only
of
protein
from our
both
were submitted
(Sha)
mg/I
had
myeloma
and
total
of the
of immunoglobulins,
serum
of the first patient
urine
reacted
revealed
that
IgE
anti-IgE
compare
the isolated
IgE myeloma
IgE protein
of the previous
cases
globulin
band
alkylated
classes
the
1gM
the
mg of IgG, 40 mg of IgA, and
detectable.
Serum
electrophoresis,
160
with
of
25%
gel electrophoresis
a monoclonal
reduced
contained
IgD
was
for
representing
ml. Starch
g/100
revealed
chain
mobility
y
2.0
Screen
heating
were
tests
of ace-
negative.
DISCUSSION
Laboratory
of
IgE
multiple
and
bone
myeloma
marrow
in
studies
patient
Hea.
conclusively
established
Her
contained
#{149}
the
diagnosis
a monoclonal
I
..
0
0
serum
..
A
Fig. 3. (A) Double
diffusion
analysis
Hea (Hea) as compared
to IgE myeloma
of classes
yG, yA, yM and yD, using
N.D. (aE). Each well contains
purified
(B) Double
diffusion
analysis
of isolated
chain antisera.
Two human
G myeloma
used as reference
proteins
(kyG,
X7G).
.
B
in agar of isolated
IgE myeloma
protein
protein
Sha (Sha) and myeloma
proteins
an antiserum
to IgE myeloma
protein
proteins
at concentration
of 1 mg/mI.
IgE myeloma
protein
(H. yE) and urine
proteins
of k and X light chain type are
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
366
FISHKIN
protein
that
reacted
specifically
to the
myeloma.
IgE myelorna
A histologic
ically
identical
IgE multiple
required
to make
tiated
by
the
to the
marrow
myeloma
The
data
the
relatively
low
and
serum
the
and
a diagnosis
in the
Sha
the
serum
was
the
was
antigen-
further
substan-
quadriceps
femoris
clinical
combination
of
three unsuccessful
efforts
of idiopathic
case
type,
under
myelofibrosis
had
ties, and were
manifestations
and
a high
serum
plasma
cell
of the male
of multiple
of the
of IgE
absence
sex. However,
myeloma-either
a number
of
Hea
the
evolution
paraprotein,
of
patients
heavy
skeletal
Bence
abnormali-
all three
cases
had some
plasma
cell leukemia5
uncommon
or osteo-
lesions.’2’3
Sclerotic
lesions
of the skeleton
unrelated
to therapy
or fractures
are
common
in multiple
rnyeloma.123
The
sclerosis
may
be circumscribe4’4
diffuse’3
and
local’5
or widespread.’3
Lucencies
may
form
the core
of
sclerotic
foci or be independent
of them.’2
A Guillain-Barr#{233}-like
syndrome4O
has
Hea
occasionally
had diffuse
Langley
et
disease
process
imately
Hea,
a
Bence
By contrast,
of visible
re-
had
of overt
blood,
sex.
first
reported
Patient
absence
female
concentration
leukemia,
in
1).
paraprotein,
the
previously
(Table
peripheral
was
represents
both
differed
cases
of IgE
Hea
as
discussion
reported
concentration
lesions,
of patient
light-chain
type.
a leukoerythroblastic
proteinuria,
sclerotic
evidence
of myeloma,
hepatosplenomegaly,
previously
osteosclerotic
Jones
and
reported
case (Sha)
of
iliac crest
biopsy
was
that
in
present
of
two
proteinuria,
N.D.
myeloma
invasive
suggested
protein
clinical
diffuse
biopsy
anemia,
antiserum
second
of an
myeloma
IgE myeloma
of
proteins
were
of
from
Jones
anti-IgE
carcinoma.
recognized
IgE myeloma
spects
an
protein
of the
examination
of multiple
of
aspirations
or metastatic
The
diagnosis
demonstration
muscles.
Prior
leukoerythroblastic
at bone
the
with
ET AL.
been
observed
in patients
with
widespread
osteoscierotic
lesions
al.’3
5-6
These
rather
mo
after
however,
meiphalan
Moreover,
of therapy
likely
related
changes
than
the
local
were
therapy.
likely
Recalcification
institution
sclerosis
most
circumscribed
as reported
of urethane’8
became
apparent
to the
underlying
1. Clinical
by
is not
evident
the
80
days
after
ND.
Sha
Hea
(yr)
Patients
screen
tLytic bone lesions
Osteosclerosis.
tests;
M-Spike
(g/100
With IgE Multiple
4.5
7.5
2.7
positive
immunochemical
found
at autopsy.
Bence
chain
ml)
50
60
65
M
M
F
approx-
therapy.
the
first
Type
Jones
Proteinuria
extensively.
the absence
was most
Myeloma
Plasma
cell
Leukemia
X
+
+
x
+
+
K
detection.
In
dose
disease.
Data of Three
Age
5ex
foci.
and
underlying
until
or melphalan’9
Light
Patients
*Negative
induced
and then
progressed
rapidly
to involve
the skeleton
the sclerosis
became
progressively
more
intense
despite
for a period
of 6 mo which
suggests
that
the sclerosis
Table
Identification
sclerotic
Clarisse’7
by
unor
the
5keletal
Lesions
-
-t
+t
of
From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
MULTIPLE
367
MYELOMA
Serum
alkaline
osteoblastic
phosphatase
activity
is usually
the
of
lesions
trabecular
skeleton
bone
without
osteoblastic
on two occasions
in patient
despite
tionation
than
the
of
bone
The
the
myeloma
elevated
low.
ordinarily
sclerosis.
myeloma2#{176} as
examination
lack
osteo-
thickened
of ‘8F uptake
by the
with
low osteoblastic
Furthermore,
phosphatase
of
demonstrates
activity.’2
The
Hea
correspond
diffuse
alkaline
in multiple
Histologic
patients
widespread
serum
not
is
sclerotic
activity
from
skeleton
pointed
isoenzyme
toward
frac-
hepatic
rather
origin.
three
reported
uncommon
to the
tional
cases
pathophysiology
should
cases
other
of
IgE
forms
myeloma
have
of myeloma.
be available
of IgE myeloma
before
can
clinical
However,
definitive
be made.
features
that
information
statements
are
from
with
addi-
regard
to the
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From www.bloodjournal.org by guest on June 17, 2017. For personal use only.
1972 39: 361-367
IgE Multiple Myeloma: A Report of the Third Case
Ben G. Fishkin, Natalie Orloff, Louis E. Scaduto, David T. Borucki and Hans L. Spiegelberg
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